Assessing intra-cardiac activation patterns and electrical dyssynchrony

ABSTRACT

Techniques for evaluating cardiac electrical dyssynchrony are described. In some examples, an activation time is determined for each of a plurality of torso-surface potential signals. The dispersion or sequence of these activation times may be analyzed or presented to provide variety of indications of the electrical dyssynchrony of the heart of the patient. In some examples, the locations of the electrodes of the set of electrodes, and thus the locations at which the torso-surface potential signals were sensed, may be projected on the surface of a model torso that includes a model heart. The inverse problem of electrocardiography may be solved to determine electrical activation times for regions of the model heart based on the torso-surface potential signals sensed from the patient.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/482,053 filed on May 3, 2011, the entire content of which isincorporated herein by reference.

TECHNICAL FIELD

The disclosure relates to electrophysiology and, more particularly, toevaluating the electrical activation patterns of the heart.

BACKGROUND

The beat of the heart is controlled by the sinoatrial node, a group ofconductive cells located in the right atrium near the entrance of thesuperior vena cava. The depolarization signal generated by thesinoatrial node activates the atrioventricular node. Theatrioventricular node briefly delays the propagation of thedepolarization signal, allowing the atria to drain, before passing thedepolarization signal to the ventricles of the heart. The coordinatedcontraction of both ventricles drives the flow of blood through thetorso of a patient. In certain circumstances, the conduction of thedepolarization signal from the atrioventricular node to the left andright ventricles may be interrupted or slowed. This may result in adyssynchrony in the contraction of the left and right ventricles, andeventually in heart failure or death.

Cardiac Resynchronization Therapy (CRT) may correct the symptoms ofelectrical dyssynchrony by providing pacing therapy to one or bothventricles or atria, e.g., by providing pacing to encourage earlieractivation of the left or right ventricles. By pacing the contraction ofthe ventricles, the ventricles may be controlled so that the ventriclescontract in synchrony. Some patients undergoing CRT have experiencedimproved ejection fraction, increased exercise capacity, and an improvedfeeling of well-being.

Providing CRT to a patient may involve determining whether the patientwill derive benefit from the CRT prior to implantation of a cardiacrhythm device, determining optimal site for placement of one or moreventricular pacing leads, and programming of device parameters, such asselection of electrodes on multi-polar right or left ventricular leads,as well as selection of the timing of the pacing pulses delivered to theelectrodes, such as atrioventricular (A-V) and intra-ventricular (V-V)delays. Assessment of electrical dyssynchrony for these purposes hastypically involved assessing QRS duration clinically. Though CRT isrecommended typically for patients with wide QRS duration, hemodynamicimprovements through CRT have been reported in narrow QRS heart failurepatients. Thus, some patients who may benefit from CRT may not beprescribed CRT based on present electrical dyssynchrony evaluationtechniques.

SUMMARY

In general, the disclosure is directed towards techniques for evaluatingelectrical dyssynchrony of the heart of a patient. The evaluation ofelectrical dyssynchrony may facilitate patient selection for CRT. Theevaluation of electrical dyssynchrony may also facilitate placement ofimplantable leads, e.g., one or more left ventricular leads, andprogramming of device parameters for CRT during an implantationprocedure, or reprogramming of device parameters for CRT during afollow-up visit.

A set of electrodes may be spatially distributed about the torso of apatient. The electrodes may each sense a body-surface potential signal,and more particularly a torso-surface potential signal, which indicatesthe depolarization signals of the heart of the patient after the signalshave progressed through the torso of the patient. Due to the spatialdistribution of the electrodes, the torso-surface potential signalrecorded by each electrode may indicate the depolarization of adifferent spatial region of the heart.

In some examples, an activation time is determined for eachtorso-surface potential signal, i.e., for each electrode of the set. Thedispersion or sequence of these activation times may be analyzed orpresented to provide variety of indications of the electricaldyssynchrony of the heart of the patient. For example, isochrone orother activation maps of the torso-surface illustrating the activationtimes may be presented to user to illustrate electrical dyssynchrony ofthe heart. In some examples, values of one or more statistical indicesindicative of the temporal and/or spatial distribution of the activationtimes may be determined. Such maps and indices, or other indications ofdyssynchrony determined based on the torso-surface activation times, mayindicate electrical dyssynchrony of the heart to a user, and facilitateevaluation of a patient for CRT, and configuration of CRT for thepatient.

In some examples, the locations of all or a subset of the electrodes,and thus the locations at which the torso-surface potential signals weresensed, may be projected on the surface of a model torso that includes amodel heart. The inverse problem of electrocardiography may be solved todetermine electrical activation times for regions of the model heartbased on the torso-surface potential signals sensed from the patient. Inthis manner, the electrical activity of the heart of the patient may beestimated. Various isochrone or other activation time maps of thesurface of the model heart may be generated based on the torso-surfacepotential signals sensed on the surface of the torso of the patient.Further, values of one or more indices indicative of the temporal and/orspatial distribution of the activation times on model heart may bedetermined. These measures and representations of electricaldyssynchrony may be used to evaluate the suitability of the patient forCRT, adjust the positioning of the CRT leads during implantation, anddetermine which electrodes of one or more multi-polar leads should beutilized for delivery of CRT, as well as the timing of pacing pulses,such as atrio-ventricular (A-V) and intra-ventricular (V-V) delays fordelivery of CRT to the patient.

For example, the one or more indications of dyssynchrony may bedetermined or generated based on data collected both during intrinsicconduction and during CRT. The degree of dyssynchrony during intrinsicconduction and CRT may be compared, e.g., to determine whether a patientis a candidate for CRT. Similarly, the one or more indications ofdyssynchrony may be determined or generated based on data collectedduring CRT with different lead positions, different electrodeconfigurations, and/or different CRT parameters, e.g., A-V or V-V delay.The change in dyssynchrony attributable to these different leadpositions, different electrode configurations, and/or different CRTparameters may be evaluated.

In one example, a method comprises receiving, with a processing unit, atorso-surface potential signal from each of a plurality of electrodesdistributed on a torso of a patient. The method further comprises for atleast a subset of the plurality of electrodes, calculating, with theprocessing unit, a torso-surface activation time based on the signalsensed from the electrode, and presenting, by the processing unit, to auser, an indication of a degree of dyssynchrony of the torso-surfaceactivation times via a display.

In another example, a system comprises a plurality of electrodesdistributed on a torso of a patient, and a processing unit. Theprocessing unit is configured to receive a torso-surface potentialsignal from each of the plurality of electrodes, calculate, for at leasta subset of the plurality of electrodes, a torso-surface activation timebased on the signal sensed from the electrode, and present, to a user,an indication of a degree of dyssynchrony of the torso-surfaceactivation times via a display.

In another example a computer-readable storage medium comprisesinstructions that, when executed, cause a processor to receive atorso-surface potential signal from each of a plurality of electrodesdistributed on a torso of a patient, calculate, for at least a subset ofthe plurality of electrodes, a torso-surface activation time based onthe signal sensed from the electrodes, and present to a user, anindication of a degree of dyssynchrony of the torso-surface activationtimes via a display.

The details of one or more aspects of the disclosure are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages will be apparent from the description anddrawings, and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a conceptual diagram illustrating an example system that maybe used to provide CRT to a heart of a patient.

FIG. 2 is a timing diagram showing an example ECG tracing of two healthyheart beats.

FIG. 3 is a timing diagram showing an example ECG tracing of a patientsuffering from left bundle branch block.

FIGS. 4A and 4B are conceptual diagrams illustrating example systems formeasuring torso-surface potentials.

FIG. 5 is a block diagram illustrating an example system for measuringtorso-surface potentials.

FIG. 6 is a series of simulated isochrone maps of torso-surfaceactivation times for typical left bundle branch block intrinsic rhythmand CRT pacing.

FIG. 7 is a flow diagram illustrating an example operation of a systemto provide indications of the cardiac electrical dyssynchrony of apatient based on torso-surface activation times.

FIG. 8 is a flow diagram illustrating an example technique forprescribing and configuring CRT based on an assessment cardiacelectrical dyssynchrony of a patient via the torso-surface activationtimes.

FIG. 9 is a series of isochrone maps of cardiac activation timesconstructed with two different heart-torso models using body-surface ECGdata from the same patient.

FIG. 10 is a flow diagram illustrating an example operation of a systemto measure the cardiac electrical dyssynchrony of a patient via thecardiac activation times.

FIG. 11 is a flow diagram illustrating an example technique forconfiguring CRT based on an assessment of cardiac electricaldyssynchrony of a patient via the cardiac activation times.

DETAILED DESCRIPTION

FIG. 1 is a conceptual diagram illustrating an example system that maybe used to provide CRT to heart 10 of patient 1. The system may includean implantable medical device (IMD) 100. IMD 100 may be a CRT pacemakeror CRT defibrillator. IMD 100 may be equipped with one or more leads;leads 102, 104, and 106; that are inserted into or on the surface of theleft ventricle 12, right ventricle 14, or right atrium 16 of heart 10.Leads 102, 104, and 106 may be equipped with one or more electrodes 108,110, and 112.

Heart 10 may suffer from an electrical dyssynchrony. Electricaldyssynchrony may occur when the depolarization signals that start thecontraction of ventricles 12 and 14 do not reach the ventricles in acoordinated manner, and results in an inefficient pumping action ofheart 10. Patient 1 may experience symptoms of heart failure. Electricaldyssynchrony may be caused by damage to the electrical system of heart10, e.g., a bundle branch block or damage to the fascicle of heart 10.Alternate conduction pathways may form within heart 10, but thesepathways may slow the progress of the electrical depolarization signaland result in the asynchronous contraction of ventricles 12 and 14.

IMD 100 may provide CRT stimulation to heart 10 of patient 1. IMD 100 isdepicted as being configured to deliver stimulation to right atrium 16,right ventricle 14, and left ventricle 12 of heart 10. In otherexamples, IMD 100 may be configured to deliver stimulation to otherportions of heart 10 depending on the condition of patient 1. IMD 100may interact with an external programmer (not shown) to adjust operatingcharacteristics, such as A-V and V-V delays, of the therapy delivered byIMD 100. In some examples, IMD 100 may also be configured to sense theelectrical activity of heart 10 through the electrodes on one or more ofleads 102, 104, and 106.

As shown in FIG. 1, leads 102, 104, 106 may extend into the heart 10 ofpatient 1 to deliver electrical stimulation to heart 10 and synchronizethe contraction of ventricles 12 and 14. Right ventricular lead 106extends through one or more veins (not shown), the superior vena cava(not shown), and right atrium 16, and into right ventricle 14. Leftventricular coronary sinus lead 102 extends through one or more veins,the vena cava, right atrium 16, and into the coronary sinus (not shown)to a region adjacent to the free wall of left ventricle 12 of heart 10.Right atrial lead 104 extends through one or more veins and the venacava, and into the right atrium 16 of heart 10.

In other configurations, IMD 100 may be equipped with more or fewerleads, depending on the requirements of the therapy provided topatient 1. For example, IMD 100 may be equipped with leads that extendto greater or fewer chambers of heart 10. In some example, IMD 100 maybe equipped with multiple leads that extend to a common chamber ofheart, e.g., multiple leads extending to the left ventricle 12. IMD 100may also be equipped with one or more leads that are placed on the heartthrough other means providing access to the cardiac tissue, such assurgical epicardial lead placement, and other pericardial accessapproaches. In some examples, IMD 100 may be equipped with a leftventricular lead that is placed on the heart endocardially.Additionally, although illustrated as implanted on the right side ofpatient 1 in FIG. 1, IMD 100 may in other examples be implanted on theleft side of the pectoral region of the patient, or within the abdomenof the patient.

Electrodes 108, 110, and 112 may attach to portions of heart 10 toprovide electrical stimulation or sense the electrical depolarizationand repolarization signals of heart 10. Electrode 108, in rightventricle 14, may be affixed to the wall of heart 10 via a screw basedmechanism. Electrode 110 may comprise multiple electrodes mounted thesame lead, allowing lead 102 to both transmit therapeutic shocks as wellas electrical sense data detected by electrode 110. Electrodes 110 and112 may be attached to the surface of heart 10 via glue, barbs, oranother permanent or semi-permanent attachment mechanism.

FIG. 2 is a timing diagram showing an example ECG tracing 200 inconjunction with certain periods or phases of the mechanical cardiaccycle. The depiction and associated description of FIG. 2 aregeneralized in the sense that the relationship between the timing ofelectrical and mechanical events is not necessarily as described for allsubjects, or at all times for any given subject.

ECG tracing 200 depicts the electrical signal of two example healthycardiac cycles. The electrical signal of a healthy heart comprises aseries of 5 characteristic waves: the P-wave, Q-wave, R-wave, S-wave,and T-wave. Each of these waves, and the intervals between them,correspond to discrete events in the functioning of a healthy heart.

In general, at some point during period 202, which stretches from thepeak of a P-wave to the peak of the subsequent R-wave, atrial systoleoccurs, which is the contraction of the atria that drives blood from theatria into the ventricles. Period 204, from the peak of the R-wave tothe opening of the aortic valve, generally marks a period ofisovolumetric contraction. The atrioventricular and aortic valves areclosed, preventing blood flow and leading to an increase in pressure inthe ventricles but not yet in the aorta. Period 206, bounded by theopening and closing of the aortic valves is generally when ejectionoccurs during the cardiac cycle. During ejection period 206 theventricles contract and empty of blood, driving the blood intocardiovascular system. As the contraction of the ventricles complete,the pressure of the blood within the cardiovascular system closes theaortic valves. Period 208, bounded by the closing of the aortic valvesand the opening of the atrioventricular valves, is the isovolumetricrelaxation of the ventricles. Periods 210 and 212 are collectively knownas the late diastole, where the whole heart relaxes and the atria fillwith blood. Period 210 corresponds to a rapid inflow of blood whileperiod 212 corresponds to diastasis, the period of slower flow bloodinto the atria before the atrial systole 202 occurs again.

The P-wave marks the stimulation of the atria and the beginning of thecardiac cycle. The atria contract under the stimulation, forcing bloodinto the ventricles. The PR segment marks the delay as thedepolarization signal travels from the atrioventricular node to thePurkinje fibers. The Q-wave marks the depolarization of theinterventricular septum as an initial part of the depolarization of theventricles. The R-wave follows the Q-wave and represents thedepolarization of the ventricles. The S-wave follows the R-wave andrepresents the later depolarization of the ventricles. The T-wave marksthe recovery and repolarization of the ventricles in preparation for thenext beat of the heart.

The QRS complex, spanning from the beginning of the Q-wave to the end ofthe S-wave, represents the electrical activation of the myocardium.Ventricular contraction of both the left and right ventricles is inresponse to the electrical activation. The QRS complex typically lastsfrom 80 to 120 ms. The relatively large amplitude of the QRS complex isdue to the large muscle mass of the ventricles. Issues affecting thesynchrony of the ventricular contraction may be demonstrated in thedeformation of the QRS complex. For example, electrical dyssynchrony inthe contraction of the ventricles can widen the R-wave or produce twoR-wave peaks, typically labeled the r-wave and R′-wave, corresponding tothe depolarization of each ventricle. The S-wave and the T-wave may bemorphological different than in an ECG tracing of a healthy heart.

FIG. 3 is a timing diagram showing ECG tracing 300. ECG tracing 300depicts the electrical signal of a patient suffering from a left bundlebranch block. A sign of the condition is the presence of an rS complexversus the typical QRS complex, though other variations of Q, R, and Swaves form combinations that may be present in patients suffering from aleft bundle branch block, right bundle branch blocks, or otherventricular conduction conditions. The extended duration of the rScomplex indicates an extended ventricular contraction time, likely dueto electrical dyssynchronies.

Diagnosis of a left or right bundle branch block, or cardiac electricaldyssyncrony in general, typically involves measuring the duration of theQRS complex (or other complex marking the depolarization of theventricles). QRS complexes lasting 100 ms or longer may indicate apartial bundle branch block and 120 ms or longer a complete bundlebranch block. In FIG. 3, the initial Q-wave is not visible, instead thetracing shows an initial r-wave, corresponding to the initialdepolarization of the right ventricle and followed by an S-wave markingthe rapid depolarization of both ventricles after the cardiac signal hasreached the left ventricle after traveling through the myocardium of theheart, rather than through the bundle branches. Because the myocardiumconducts electricity more slowly than the bundle branches, the entirecomplex is spread out over a longer period.

Absent a case of bundle branch block—such as the one shown in FIG. 3—orother condition, diagnosis may be more challenging. Occultdyssynchronies may be present that, while responsive to CRT, may not bereadily identifiable from an examination of the typical 12-lead ECG.These occult dyssynchronies may manifest in the electrical signalsgenerated by the heart and measured on the surface of the torso and maybe diagnosable through alternative means of analysis, such as bydetermining cardiac activation times at a plurality of spatiallydistributed locations according to the techniques described herein.

FIGS. 4A and 4B are conceptual diagrams illustrating example systems formeasuring body-surface potentials and, more particularly, torso-surfacepotentials. In one example illustrated in FIG. 4A, sensing device 400A,comprising a set of electrodes 404A-F (generically “electrodes 404”) andstrap 408, is wrapped around the torso of patient 1 such that theelectrodes surround heart 10. As illustrated in FIG. 4A, electrodes 404may be positioned around the circumference of patient 1, including theposterior, lateral, and anterior surfaces of the torso of patient 1. Inother examples, electrodes 404 may be positioned on any one or more ofthe posterior, lateral, and anterior surfaces of the torso. Electrodes404 may be electrically connected to processing unit 500 via wiredconnection 406. Some configurations may use a wireless connection totransmit the signals sensed by electrodes 404 to processing unit 500,e.g., as channels of data.

Although in the example of FIG. 4A sensing device 400A comprises strap408, in other examples any of a variety of mechanisms, e.g., tape oradhesives, may be employed to aid in the spacing and placement ofelectrodes 404. In some examples, strap 408 may comprise an elasticband, strip of tape, or cloth. In some examples, electrodes 404 may beplaced individually on the torso of patient 1.

Electrodes 404 may surround heart 10 of patient 1 and record theelectrical signals associated with the depolarization and repolarizationof heart 10 after the signals have propagated through the torso ofpatient 1. Each of electrodes 404 may be used in a unipolarconfiguration to sense the torso-surface potentials that reflect thecardiac signals. Processing unit 500 may also be coupled to a return orindifferent electrode (not shown) which may be used in combination witheach of electrodes 404 for unipolar sensing. In some examples, there maybe 12 to 16 electrodes 404 spatially distributed around the torso ofpatient 1. Other configurations may have more or fewer electrodes 404.

Processing unit 500 may record and analyze the torso-surface potentialsignals sensed by electrodes 404. As described herein, processing unit500 may be configured to provide an output to a user indicating theelectrical dyssynchrony in heart 10 of patient 1. The user may make adiagnosis, prescribe CRT, position therapy devices, e.g., leads, oradjust or select treatment parameters based on the indicated electricaldyssynchrony.

In some examples, the analysis of the torso-surface potential signals byprocessing unit 500 may take into consideration the location ofelectrodes 404 on the surface of the torso of patient 1. In suchexamples, processing unit 500 may be communicatively coupled to animaging device 501, which may provide an image that allows processingunit 500 to determine coordinate locations of each of electrodes 400 onthe surface of patient 1. Electrodes 404 may be visible, or madetransparent through the inclusion or removal of certain materials orelements, in the image provided by imaging system 501.

FIG. 4B illustrates an example configuration of a system that may beused to evaluate electrical dyssynchrony in heart 10 of patient 1. Thesystem comprises a sensing device 400B, which may comprise vest 410 andelectrodes 404 A-ZZ (generically “electrodes 404”), a processing unit500, and imaging system 501. Processing unit 500 and imaging system 501may perform substantially as described above with respect to FIG. 4A. Asillustrated in FIG. 4B, electrodes 404 are distributed over the torso ofpatient 1, including the anterior, lateral, and posterior surfaces ofthe torso of patient 1.

Sensing device 400B may comprise a fabric vest 410 with electrodes 404attached to the fabric. Sensing device 400B may maintain the positionand spacing of electrodes 404 on the torso of patient 1. Sensing device400B may be marked to assist in determining the location of electrodes404 on the surface of the torso of patient 1. In some examples, theremay be 150 to 256 electrodes 404 distributed around the torso of patient1 using sensing device 400B, though other configurations may have moreor fewer electrodes 404.

FIG. 5 is a block diagram illustrating an example system for measuringtorso-surface potentials and providing indications of electricaldyssynchrony. The example system may comprise a processing unit 500 anda set of electrodes 404 on a sensing device 400, e.g., one of examplesensing devices 400A or 400B (FIGS. 4A and 4B). The system may alsoinclude an imaging system 501.

As illustrated in FIG. 5, processing unit 500 may comprise a processor502, signal processor 504, memory 506, display 508, and user inputdevice 509. Processing unit 500 may also include an electrode locationregistration module 524. In the illustrated example, processor 502comprises a number of modules and, more particularly, a projectionmodule 514, an inverse problem module 516, an activation time module518, an indices module 520, and an isochrones mapping module 522. Memory506 may store recorded data 510 and models 512.

Processing unit 500 may comprise one or more computing devices, whichmay be co-located, or dispersed at various locations. The variousmodules of processing unit 500, e.g., processor 502, projection module514, inverse problem module 516, activation time module 518, statisticsmodule 520, isochrones mapping module 522, signal processor 504,electrode location registration module 524, display 508, memory 506,recorded data 510 and torso models 512 may be implemented in one or morecomputing devices, which may be co-located, or dispersed at variouslocations. Processor 502, and the modules of processor 502, may beimplemented in one or more processors, e.g., microprocessors, of one ormore computing devices, as software modules executed by theprocessor(s). Electrode location registration module 524 may, in someexamples, be implemented in imaging system 501.

In addition to the various data described herein, memory 506 maycomprise program instructions that, when executed by a programmableprocessor, e.g., processor 502, cause the processor and any componentsthereof to provide the functionality attributed to a processor andprocessing unit herein. Memory 506 may include any volatile,non-volatile, magnetic, optical, or electrical media, such as a harddisk, magnetic tape, random access memory (RAM), read-only memory (ROM),CD-ROM, non-volatile RAM (NVRAM), electrically-erasable programmable ROM(EEPROM), flash memory, or any other digital or analog media. Memory 506may comprise one or more co-located or distributed memories. Memory 506may comprise a tangible article that acts as a non-transitory storagemedium for data and program instructions.

The torso-surface potential signals sensed by electrodes 404 of sensingdevice 400 may be received by signal processor 504 of processing unit500. Signal processor 504 may include an analog-to-digital converter todigitize the torso-surface potential signals. Signal processor 504 mayalso include various other components to filter or otherwise conditionthe digital signals for receipt by processor 502.

Electrode location registration module 524 may receive imaging data fromimaging system 501. Electrode location registration module 524 analyzesthe imaging data. In particular, electrode registration location module524 identifies electrodes 404, or elements co-located with theelectrodes that are more clearly visible via the imaging modality,within the images. Electrode location registration module 524 mayfurther identify the locations of each of the electrodes on the surfaceof the patient and/or within a three-dimensional coordinate system. Insome examples, the locations of electrodes 404 may be manuallyidentified and registered with processing unit 500, e.g., by a user, viaelectrode registration module 524.

The imaging data may comprise data representing one or more images ofpatient 1 wearing electrodes 404, e.g., of a sensing device 400. In someexamples, the images may be obtained before or during a medicalprocedure, e.g., a surgical procedure to implant a cardiac rhythm deviceand lead system for delivery of CRT.

In some examples, processor 502 may store the torso-surface potentialsignals, imaging data from imaging system, electrode location data fromelectrode location registration module, or any values disclosed hereinthat are derived by processing of such signals and data by processor502, within memory 506 as recorded data 510. Each recorded torso-surfacepotential signal, or other values derived therefrom, may be associatedwith a location of the electrode 404 that sensed the torso-surfacepotential signal. In this manner, the torso-surface potential data maybe correlated with the position of electrodes 404 on the torso ofpatient 1, or within a three-dimensional coordinate system, enablingspatial mapping of the data to particular locations on the surface ofthe torso or within the coordinate system. In some examples, aspects ofthe techniques described herein may be performed at some time after theacquisition of the torso-surface potential signals and location databased on recorded data 510.

Processor 502 may be configured to provide one or more indications ofelectrical dyssynchrony based on the torso-surface potential signalsand, in some examples, the electrode location data. Example indicationsof electrical dyssynchrony include indices illustrating activation timesfor each electrode/location distributed about the torso or heart, or forone or more subsets of electrodes located within a common region, e.g.,within a left posterior, left anterior, right posterior, or rightanterior region. In some examples, processor 502 may be configured toprovide a set of two or more different indications, e.g., severaldifferent indications, for each of two or more different regions, e.g.,several different regions, of the torso or heart.

Some indications of dyssynchrony may include statistical values or otherindices derived from activation times for each electrode location or oneor more subsets of electrodes within one or more regions. Other examplesindications of electrical dyssynchrony that may be determined based onactivation times at various electrodes/locations include graphicalindications, such as an isochrone or other activation maps, or ananimation of electrical activation. Other examples indications ofelectrical dyssynchrony that may be determined based on activation timesat various electrodes/locations include identifying one of apredetermined number of dyssynchrony levels, e.g., high, medium, or low,via text or color, e.g., red, yellow, green, for example.

In some examples, the various indications of dyssynchrony for one ormore regions may be determined based on data collected at two or moredifferent times and/or under two or more different conditions. Forexample, the various indications of dyssynchrony may be determined basedon torso-potential signals collected during intrinsic conduction ofheart 10, and also determined based on torso-potential signals collectedduring CRT. In this manner, the potential dyssynchrony-reducing benefitof CRT may be evaluated for the patient by comparing the differentvalues, graphical representations, or the like, resulting from intrinsicconduction and CRT. As another example, the various indications ofdyssynchrony may be determined each of a plurality of different timesbased on torso-potential signals collected during delivery of CRT withdifferent lead positions, electrode configurations, or CRT parameters,e.g., A-V or V-V interval values. In this manner, the relativedyssynchrony-reducing benefits of the different lead positions,electrode configurations, or CRT parameters positions may be evaluatedfor the patient by comparing the different values, graphicalrepresentations, or the like.

Models 512 may include a plurality of different models, e.g.,three-dimensional models, of the human torso and heart. A model torso ormodel heart may be constructed by manual or semi-automatic imagesegmentation from available databases of previously acquired medicalimages (CT/MRI) of a plurality of subjects, e.g., cardiomyopathypatients, different than patient 1, using commercially availablesoftware. Each model may be discretized using a boundary element method.A plurality of different torso models may be generated. The differentmodels may represent different subject characteristics, such asdifferent genders, disease states, physical characteristics (e.g., largeframe, medium frame and small frame), and heart sizes (e.g., x-large,large, medium, small). By providing input via user input 509, a user mayselect from among the various model torsos and model hearts that may bestored as models 512 in memory 506, so that the user may more closelymatch the actual torso and heart 10 of patient 1 with the dimensions andgeometry of a model torso and model heart. In some examples, medicalimages of the patient, e.g., CT or MRI images, may be manually orsemi-automatically segmented, registered, and compared to models 512 forselection from amongst the models 512. Furthermore, single or multipleview 2-D medical images (e.g., x-ray, fluoroscopy) may be segmented ormeasured to determine approximate heart and torso dimensions specific tothe patient in order to select the best fit model torso and heart.

Projection module 514 may project the locations of electrodes 404, e.g.,stored as recorded data 510 within of memory 506, onto an appropriate,e.g., user-selected, model torso contained in model data module 512 ofmemory 506. By projecting the location of electrodes 404 onto the modeltorso, projection module 514 may also project the torso-surfacepotential signals of patient 1 sensed by electrodes 404 onto the modeltorso. In other examples, the measured electrical potentials may beinterpolated and resamples at electrode positions given by the model. Insome examples, projecting the torso-surface potentials onto the modeltorso may allow processor 502, via inverse problem module 516, toestimate the electrical activity of at various locations or regions ofthe model heart corresponding to heart 10 of patient 1 that produced themeasured torso-surface potentials.

Inverse problem module 516 may be configured to solve the inverseproblem of electrocardiography based on the projection of the measuredtorso-surface potentials, recorded by electrodes 404, onto the modeltorso. Solving the inverse problem of electrocardiography may involvethe estimation of potentials or activation times in heart 10 based on arelationship between the torso and heart potentials. In one examplemethod, model epicardial potentials are computed from model torsopotentials assuming a source-less volume conductor between the modelheart and the model torso in an inverse Cauchy problem for Laplace'sequation. In another example method, an analytic relationship betweentorso-surface potentials and the cardiac transmembrane potential isassumed. Torso-surface potentials may be simulated based on thisrelationship. In some examples, inverse problem module 516 may utilizetechniques described by Ghosh et al. in “Accuracy of Quadratic VersusLinear Interpolation in Non-Invasive Electrocardiographic Imaging(ECGI),” Annals of Biomedical Engineering, Vol. 33, No. 9, September2005, or in “Application of the L1-Norm Regularization to EpicardialPotential Solution of the Inverse Electrocardiography Problem,” Annalsof Biomedical Engineering, Vol. 37, No. 5, 2009, both of which areincorporated herein by reference in their entireties. In other examples,any known techniques for solving the inverse problem ofelectrocardiography may be employed by inverse problem module 516.

Activation time module 518 may compute the activation times directlyfrom measured torso-surface potentials, or by estimating modeltransmembrane potentials. In either case, an activation time for eachelectrode/location may be determined as a time period between twoevents, such as between the QRS complex onset and the minimum derivative(or steepest negative slope) of the sensed torso potential signal orestimate epicardial potential signal. Thus, in one example, cardiacactivation times are estimated from the steepest negative slope of themodel epicardial electrograms. Cardiac activation times (parameters inthe analytic relationship between torso-surface potential and cardiactransmembrane potential) may, in other configurations, be computed basedon minimizing the least square difference between the measuredtorso-surface potentials and simulated torso-surface potentials. Acolor-coded isochrone map of ventricular, epicardial, or torso-surfaceactivation times may be shown by display 308. In other examples, display308 may show a two-color animation of propagation of the activationwavefront across the surface of the model heart or the torso-surface.

Indices module 520 may be configured to compute one or more indices ofelectrical dyssynchrony from the torso-surface or cardiac activationtimes. These indices may aid in the determination of whether the patientis a candidate for CRT, placement of CRT leads, and selection of CRTparameters. For example, LV lead 102 (FIG. 1) may be positioned at thesite that reduces dyssynchrony from one or more indices or,alternatively, the largest electrical resynchronization as demonstratedby the indices. The same indices may be also used for programming A-Vand/or V-V delays during follow-up. As indicated above, the indices maybe determined based on the activation times for allelectrodes/locations, or for one or more subsets of electrodes in one ormore regions, e.g., to facilitate comparison or isolation of a region,such as the posterior and/or left anterior, or left ventricular region.

One of the indices of electrical dyssynchrony may be a standarddeviation index computed as the standard deviation of theactivations-times (SDAT) of some or all of electrodes 404 on the surfaceof the torso of patient 1. In some examples, the SDAT may be calculatedusing the estimated cardiac activation times over the surface of a modelheart.

A second example index of electrical dyssynchrony is a range ofactivation times (RAT) which may be computed as the difference betweenthe maximum and the minimum torso-surface or cardiac activation times,e.g., overall, or for a region. The RAT reflects the span of activationtimes while the SDAT gives an estimate of the dispersion of theactivation times from a mean. The SDAT also provides an estimate of theheterogeneity of the activation times, because if activation times arespatially heterogeneous, the individual activation times will be furtheraway from the mean activation time, indicating that one or more regionsof heart 10 have been delayed in activation. In some examples, the RATmay be calculated using the estimated cardiac activation times over thesurface of a model heart.

A third example index of electrical dyssynchrony estimates thepercentage of electrodes 404 located within a particular region ofinterest for the torso or heart, whose associated activation times aregreater than a certain percentile, for example the 70th percentile, ofmeasured QRS complex duration or the determined activation times forelectrodes 404. The region of interest may be a posterior, leftanterior, and/or left-ventricular region, as examples. This index, thepercentage of late activation (PLAT), provides an estimate of percentageof the region of interest, e.g., posterior and left-anterior areaassociated with the left ventricular area of heart 10, which activateslate. A large value for PLAT may imply delayed activation of substantialportion of the region, e.g., the left ventricle 12 (FIG. 1), and thepotential benefit of electrical resynchronization through CRT bypre-exciting the late region, e.g., of left ventricle 12. In otherexamples, the PLAT may be determined for other subsets of electrodes inother regions, such as a right anterior region to evaluate delayedactivation in the right ventricle. Furthermore, in some examples, thePLAT may be calculated using the estimated cardiac activation times overthe surface of a model heart for either the whole heart or for aparticular region, e.g., left or right ventricle, of the heart.

Isochrone module 522 may be configured to generate an isochrone mapdepicting the dispersion of activation times over the surface of thetorso of patient 1 or a model heart. Isochrone module 522 mayincorporate changes in the torso-surface or cardiac activation times innear real-time, which may permit near instant feedback as a user adjustsa CRT device or monitors patient 1 to determine if CRT is appropriate.Isochrone maps generated by isochrone module 522 may be presented to theuser via display 508.

In general, processor 502 may generate a variety of images or signalsfor display to a user via display 508 based on the measuredtorso-surface potentials, calculated torso-surface or estimated cardiacactivation times, or the degree of change in electrical dyssynchrony.For example, a graded response reflecting the efficacy of a particularlocation of the LV lead 102 during biventricular pacing or singleventricle fusion pacing may be provided to the physician in terms of ared, yellow and green signal. A red signal may be shown if the reductionin electrical dyssynchrony during CRT pacing compared to intrinsicrhythm is negative (an increase in electrical dyssynchrony) or minimal,e.g., less than 5%. A yellow signal may be triggered if there is somereduction in electrical dyssynchrony during CRT pacing compared tointrinsic rhythm, for example between 5% and 15%, but there may bepotentially better sites for lead placement. If the reduction inelectrical dyssynchrony during CRT pacing compared to intrinsic rhythmis substantial, e.g., greater than 15%, a green signal may be triggeredindicating to the physician that the present site provides effectivechanges in synchronization. The feedback from this system in combinationwith other criteria (like magnitude of pacing threshold, impedance,battery life, phrenic nerve stimulation) may be also used to choose anoptimal pacing vector for one or more multipolar leads. The feedbackfrom this system may be also used for selecting optimal device timings(A-V delay, V-V delay, etc) influencing the extent of fusion ofintrinsic activation with paced activation from single or multipleventricular sites, or discerning acute benefit of single site fusionpacing versus multi-site pacing and choice of appropriate pacing type.

Display 508 may also display three-dimensional maps of electricalactivity over the surface of the torso of patient 1 or over a modelheart. These maps may be isochrone maps showing regions of synchronouselectrical activity as the depolarization progresses through heart 10 ofpatient 1. Such information may be useful to a practitioner indiagnosing asynchronous electrical activity and developing anappropriate treatment, as well as evaluating the effectiveness of thetreatment.

FIG. 6 is a series of simulated isochrone maps 600 of torso-surfaceactivation times over the torso of a patient suffering from anelectrical dyssynchrony in the left ventricle before and duringtreatment with a CRT device. The isochrone maps before (intrinsic) andafter treatment are divided into two views: anterior and posterior. Line602 represents the location of a subset of electrodes 404, e.g., asubset of electrodes 404 of sensing device 400B, that may be used tocalculate one or more indices of electrical dyssynchrony. In someexamples, line 602 may represent electrodes 404 on sensing device 400A.

The isochrone maps 600 of the natural and CRT assisted torso-surfaceactivation times may be generated using multiple electrodes 404distributed over the surface of the torso of a patient, e.g., usingsensing device 400B. Generation of the isochrone maps 600 may includedetermining the location of electrodes 404, and sensing torso-surfacepotential signals with the electrodes. Generation of the isochrone maps600 may further include calculating the torso-surface activation timefor each electrode or electrode location by determining the point in therecorded QRS complex of the signal sensed by the electrodescorresponding to the maximum negative slope. In other examples, thetorso-surface activation times may be determined by identifying theminimum derivative of the QRS complex. The measured torso-surfaceactivation times may then be standardized and an isochrone map of thesurface of the torso of the patient generated.

The delayed activation of certain locations associated with certain onesof electrodes 404 due to the electrical dyssynchrony is apparent in theposterior views of the intrinsic torso-surface activation times. Regions604 indicate increased delay in the activation of the underlying heart.The corresponding posterior view during treatment with a CRT deviceindicate that regions 606, the same location as regions 604 on the mapsof intrinsic torso-surface activation times, exhibits increasedsynchrony in electrical ventricular activity. The CRT maps exhibitdecreased range and a lower standard deviation of torso-surfaceactivation times. Further, the posterior regions no longer exhibitdelayed activation times. The isochrone map of the torso-surfaceactivation times during intrinsic and CRT pacing and changes indistribution of activation-times from intrinsic to CRT pacing may beused for diagnostic purposes or the adjustment of a CRT device.

One or more indices of electrical dyssynchrony may also be calculatedfrom the torso-surface activation times used to generate isochrone maps600. For example, SDAT, an indication of the spread of the activationtimes, for the patient's intrinsic heart rhythm using the complete setof electrodes 404 is 64. Using the reduced lead set marked by line 602results in an SDAT of 62. The RAT for the intrinsic heart rhythm andcomplete lead set is 166.5 while the reduced lead set has a RAT of 160.PLAT for the intrinsic heart rhythm using the reduced and complete leadsets are 56.15% and 66.67%, respectively. This indicates that using areduced lead set that circumscribes the heart of the patient, e.g.,sensing device 400A and associated electrodes 404, may providecomparable indices of electrical dyssynchrony compared to using anelectrode set covering the torso of the patient, such as sensing device400B.

The indices of electrical dyssynchrony also provide indication of theeffectiveness of the CRT device, with the SDAT for the reduced set ofelectrodes declining to 24, the RAT to 70 and PLAT to 36%. Thisindicates that the torso-surface activation times during CRT treatmentwere more narrowly distributed and in a smaller range than in the normalheart rhythm and that the percentage of electrodes 404 located on theleft anterior surface of the torso of the patient registering lateactivation times decreased markedly.

FIG. 7 is a flow diagram illustrating an example operation of a systemto evaluate the cardiac electrical dyssynchrony of a patient via thetorso-surface activation times. The location of electrodes, e.g.,electrodes 404 (FIGS. 4A and 4B), distributed over the surface of thetorso of the patient may be determined (700). A cardiac event, e.g., adepolarization, may generate an electrical signal that propagatesthrough the torso of a patient, e.g., patient 1 (FIG. 1) and registerson the electrodes. The signal sensed by the electrodes may be received(702), e.g., by processing unit 500 (FIG. 5). The processing unit maycalculate the torso-surface activation times (704). In some examples,the processing unit may also construct a torso-surface activation timesisochrone map (706). The processing unit may also calculate at least oneindex of cardiac electrical dyssynchrony (708). These indices maycomprise one or more of the SDAT (710), RAT (712), and the PLAT (714).

A cardiac event, such as a depolarization, generates an electricalsignal that propagates through the torso. The electrical signal maycomprise a QRS complex, or a variant caused by a heart related conditionsuch as a left or right bundle branch block. The electrical signal maynot propagate uniformly through the torso of a patient due to variationsin conductivity within the torso and the heart. These delays maymanifest in electrodes distributed over the surface of the torso of thepatient registering the same electrical signal at different points intime.

The electrical signal generated by the cardiac event may register on theplurality of electrodes distributed over the surface of the torso ofpatient. The electrodes may be distributed over the anterior, lateral,and/or posterior surfaces of the torso, allowing the generation of athree-dimensional picture of the electrical activity occurring withinthe torso. In some examples, the electrodes may be placed to provideextensive coverage both above and below the heart, e.g., by usingsensing device 400B (FIG. 4B). In other examples, a reduced set ofelectrodes may be arranged around the circumference of the torso,circumscribing the heart of the patient, e.g., using sensing device 400A(FIG. 4A). The electrodes may receive the complete waveform of theelectrical signal generated by the cardiac event, and transmit thesignal to a processing unit.

The location of electrodes distributed over the surface of the torso ofthe patient may be determined (700). Locating the electrodes may beperformed automatically, e.g. by imaging system 501 and electrodelocation registration module 524 of processing unit 500 (FIG. 5). Theelectrodes may be located by analyzing one or more images of the torsoof a patient and performing a pattern matching routine, e.g.,recognizing the shape of an electrode against the torso of the patient,and storing the location of the electrode on the torso of the patient inprocessing unit memory. In other examples, the location of sensingdevice 400A or 400B may be determined and the locations of theelectrodes determined based on the position of the sensing device, e.g.,basing the position of the electrode on the patient through the knownposition of the electrode on the sensing device. In another example, theposition of the electrodes may be measured manually.

The processing unit may receive the electrical signal from theelectrodes and record the output in memory (702). The processing unitmay record the raw output, e.g., the raw ECG tracing from eachelectrode, as well as location data for the electrodes, allowing theelectrical signals detected by the electrodes to be mapped onto thesurface of the torso of the patient.

The processing unit may compute the torso-surface activation times(704). A processor, e.g., processor 502 of processing unit 500 (FIG. 5),may retrieve ECG tracing data stored within the processing unit memoryand analyze the tracing to detect depolarization of the ventricles ofthe heart, typically marked by a QRS complex in the tracing. Theprocessor may, in some examples, detect ventricular depolarization bydetermining the time of the minimum derivative (or steepest negativeslope) within the QRS complex measured with respect to the time of QRScomplex onset. The determination of the activation time may be made foreach electrode and stored in the processing unit memory.

In some configurations, the processing unit may construct an isochronemap of the torso-surface activation times, allowing the user to visuallyinspect the propagation of the electrical signals of the heart afterprogression through the torso of the patient. The isochrone map may beconstructed by dividing the range of measured torso-surface activationtimes into a series of sub-ranges. The location of each electrode on thesurface of the torso of the patient may be graphically represented.Regions of electrodes whose measured activation times fall within thesame sub-range may be represented by the same color on the graphicalrepresentation.

The processing unit may also calculate one or more indices of electricaldyssynchrony based on the torso-surface activation times (708). Theseindices may include the SDAT (710), RAT (712), and PLAT (714). In someexamples, the PLAT may be determined as the percentage of posteriorelectrodes activating after a certain percentage of the QRS complexduration.

As discussed above, in some examples, the construction of atorso-surface activation times isochrone map (706), or other graphicalrepresentation of dyssynchrony, as well as the calculation of indices ofelectrical dyssynchrony (708), may be performed for a particular regionof the torso based the signals received from electrodes (702) in suchregions. Graphical representations and indices of electricaldyssynchrony may be determined for each of a plurality of regions basedon the signals received from the electrodes for such regions. In someexamples, the representations and indices for various regions may bepresented together or compared.

FIG. 8 is a flow diagram diagram illustrating an example technique formeasuring the cardiac electrical dyssynchrony of a patient via measuredtorso-surface activation times. A processing unit 500 may receivetorso-surface potential signals from a plurality of electrodes (800),e.g., electrodes 404 (FIGS. 4A and 4B). The processing unit 500 maycalculate the torso-surface activation times for each of the pluralityof electrodes (802). The processing unit 500 may provide at least oneindication of cardiac electrical dyssynchrony (804).

A user may evaluate the whether a patient is a candidate for CRT basedon the at least one indication of electrical dyssynchrony (806). Theuser may also monitor the at least one indication of electricaldyssynchrony (808), and use the changes in the at least one indicationto aid in adjusting the positioning of electrodes, e.g., electrodes 108,110, and 112 (FIG. 1), during implantation of a CRT device (810), e.g.,IMD 100 (FIG. 1), or selection of the various programmable parameters,such as electrode combination and the A-V or V-V pacing intervals, ofthe CRT device (812), during implantation or a follow-up visit.

The various indications of cardiac electrical dyssynchrony describedherein, such as statistical or other indices, or graphicalrepresentations of activation times, may indicate the presence of damageto electrical conductivity of the heart of the patient, for example thepresence of a left or right bundle branch block, that may not beapparent from the examination of a standard 12-lead ECG readout. Forexample, a large SDAT indicates that the activation of the ventricles isoccurring over a large time span, indicating that the depolarization ofthe ventricles is not occurring simultaneously. A large RAT alsoindicates a broad range of activation times and asynchronous contractionof the ventricles. A high PLAT indicates that a specific region of theheart, e.g., the posterior regions associated with the left ventricle,may be failing to activate in concert with the measured QRS complex.Additionally, by monitoring the at least one indication of cardiacelectrical dyssynchrony, the user may detect changes in the electricalactivity of the heart caused by different treatments or treatmentconfigurations.

As described above, the various indications of electrical dyssynchrony,such as statistical indexes, may be calculated for each of a pluralityof regions, e.g., posterior, left anterior, or the like, based ontorso-surface activations times from the region. Additionally,evaluating whether a patient is a candidate for CRT based on the atleast one indication of electrical dyssynchrony (806) may includedetermining the one or more indications of electrical dyssynchrony basedon torso-surface activation times both during intrinsic conduction ofthe heart, and during CRT. Differences between the indications duringintrinsic conduction and CRT may indicate that CRT would provide benefitfor the patient, e.g., that the patient is a candidate for CRT. Asdescribed above, the user may also evaluate whether a patient is acandidate for CRT based on at least one indication of electricaldyssynchrony based on intrinsic rhythm alone. Furthermore, monitoringthe at least one indication of electrical dyssynchrony (808) duringimplantation or a follow-up visit may include determining the one ormore indications of electrical dyssynchrony for each of a plurality oflead positions, electrode configurations, or other parameter valuesbased on torso-surface activation times resulting from delivery of CRTat the positions, or with the electrode configurations or parametervalues. In this manner, differences between dyssynchrony indicationsassociated with various locations, electrode configurations, orparameter values may be compared to determine preferred locations,configurations, or values.

FIG. 9 is a series of isochrone maps of cardiac activation times. Views900, 902 and 904 were constructed using torso-surface potentialsmeasured on the surface of the torso of a patient and projected ontothree dimensional models of the torso and the heart of the patient.Views 910, 912, and 914 were constructed using the measuredtorso-surface potentials of the same patient projected onto a differentmodel torso and model heart.

The three-dimensional representation of the hearts depicted in views900, 902, 904, 910, 912 and 914 were constructed using computertomography (CT) images of hearts obtained from databases of previouslyacquired cardiothoracic images. The locations of the electrodes, e.g.,electrodes 404 of sensing device 400B (FIG. 4B), on the torso of thepatient may be plotted to approximate locations on a model torso. Acomputer may be used to solve the inverse problem ofelectrocardiography, which includes determining the electrical activityon the surface of the heart that would produce the measuredtorso-surface potentials. The isochrone maps illustrated in views 900,902, 904, 910, 912 and 914 are based on images of hearts of twodifferent patients, which are also used to determine the geometry of theheart and relationship to the corresponding torso for solving theinverse problem of electrocardiography.

The model torsos and hearts may be constructed by manual orsemi-automatic image segmentation from available databases of previouslyacquired medical images (CT/MRI) of cardiomyopathy patients usingcommercially available software. Each model may be discretized usingboundary element method and may be further manipulated to account forpatients with different physical characteristics (e.g., large frame,medium frame and small frame) and heart sizes (e.g., x-large, large,medium, small).

A user may select the appropriate model torso and heart to suit thepatient, e.g., a patient having a large torso may be simulated with alarge frame model torso. In some examples, medical images of thepatient, e.g., CT or MRI images, may be manually or semi-automaticallysegmented, registered, and compared to a variety of available models forselection from amongst the models. One or more views of 2-D medicalimages (e.g., X-ray or fluoroscopy) may also be used. The user mayproject the measured torso-surface potentials from the torso of thepatient onto the corresponding locations on the model torso. The inverseproblem of propagating the electrical signals from the model torso tothe model heart may then be solved, and activation times for the modelheart may be estimated.

In one example in which the techniques of this disclosure were applied,human thoracic CT images for other subjects were obtained from imagedatabases. Semi-automatic image segmentation was performed on the imagesto generate the three-dimensional representation of the different modelsof hearts and torsos. In some examples, image segmentation may be donewith the AMIRA software package commercially-available from VisageImaging, Inc., of San Diego, Calif.

For the example, the projection of electrode locations on the patienttorso to the model torso was approximate. In particular, the locationselectrodes on the patient torso to the model torso the locations of theelectrodes on the patient torso were projected onto the surface of themodel torso based on the order in which the electrodes were mounted onthe patient. For the purpose of this projection, the patient and modeltorsos were divided into right anterior, left anterior, right posteriorand left posterior regions, using the sternum (anterior) and the spine(posterior) as references. Electrodes were arranged in vertical stripsand three strips were applied to each region of the torso. Electrodes inthese regions were projected on to the corresponding segments of themodel torso. The method described is one of many techniques that may beused to registered or map the geometrical distribution of measuredelectrical potentials. For example, the measured electrical potentials.For example, the measured electrical potentials may be interpolated andresampled at electrode positions given by the model. Projection of theelectrode locations from segments of the patient torso onto thecorresponding segments of the model torso in the correct order enabledthe activation patterns and spatial dispersion of activation on themodel heart to reflect the activation patterns and spatial dispersion ofactivation on the actual patient heart with relative accuracy. In oneexample, the inverse problem of electrocardiography may be solved usingthe Matlab regularization toolbox (Hansen PC, Regularization Tools: AMatlab package for analysis and solution of discrete ill-posed problems,Numerical Algorithms, 6(1994), pp 1-35).

Input data-sets for solving the inverse problem consistent with theexample may include multi-electrode surface ECG measurements, the 3-DCartesian coordinates of the model heart and torso surfaces, and themesh over each model surface which specified the connectivity of thedifferent points on each surface. An output consistent with thetechniques of this disclosure may include activation times on the 3-Dmodel heart surface which can be visualized using visualization softwareand computer graphics tools. In some examples, the 3-D model heartsurface may be visualized using the tools in Matlab (Mathworks Inc,Natick, Mass.) or more advanced visualization software, such as Tecplot(Tecplot Inc, Bellevue, Wash.).

Comparing estimated cardiac activation times on two different, bothcardiac activation times determined from the same torso-surfacepotential signals for one subject, show similar patterns anddistribution. For example, region 906 of views 902 and 904 correspondsin size and activation time to region 916 of views 912 and 914. Region908 of views 902 and 904 corresponds to region 918 of views 912 and 914.Additionally, the standard deviations of activations time for bothmodels are both derived from the same torso-surface potentials for onesubject, were similar (17.6 and 15.5 ms). The overall pattern of cardiacactivation and measures of dispersion of cardiac activation times arethus not dependent on a specific heart-torso model. Using a genericheart-torso model may allow a user to create an isochrone model of thecardiac activation time suitable for diagnosis and observation whileavoiding expense, inconvenience, and radiation exposure that may becaused by the CT scan or other imaging that may be used to produce apatient-specific model of the heart of the patient.

FIG. 10 is a flow diagram illustrating an example operation of a systemto measure the cardiac electrical dyssynchrony of a patient via thecardiac activation times. Processing unit 500 determines the location ofthe electrodes 404, e.g., based on an analysis of imaging data by anelectrode location registration module 524. Processing unit projects thelocations of the electrodes onto a model torso, e.g., a selected modeltorso (1002).

A cardiac event, e.g., depolarization, occurs causing an electricalsignal to propagate through the torso of the patient, and register onthe electrodes distributed on the surface of the torso of the patient.The torso-surface potential signals sensed by the electrodes may bereceived by processing unit 500 (1004). The processing unit may projectthe signals onto the surface of the model torso based on the determinedlocations of the electrodes (1006).

The processing unit may solve the inverse problem of determiningepicardial potentials based on torso-surface potentials (1008). Theprocessing unit may then calculate cardiac activation times at a varietyof locations of the model heart based upon the projected torso-surfacepotentials (1010). The cardiac activation times may be computed by, forexample, determining the greatest negative slope of the epicardialelectrogram potentials (1016) or by least squares minimization in thesolution of the inverse problem (1018). The cardiac activation time maybe displayed (1012). Examples of potential methods for displayingcardiac activation times include isochrone maps (1014) and a moviedepicting the progression of the wavefront over the model heart (1016).The processing unit may be configured to allow a user select between, ordisplay simultaneously, various display modes, including the wave frontmovie and isochrone maps. Additionally, one or more indices of cardiacelectrical dyssynchrony may be calculated (1018), including the SDAT(1020), RAT (1022), and PLAT (1024).

For solving the inverse problem (1008), epicardial potentials may becomputed from projected torso-surface potentials assuming a source-lessvolume conductor between the heart and the torso in an inverse Cauchyproblem for Laplace's equation. Alternatively, an analytic relationbetween torso-surface potentials and the cardiac transmembrane potentialmay be assumed. Additionally, cardiac activation times may be estimated(1010) from the steepest negative slope of the epicardial electrogramsdetermined from the inverse solution of the torso-surfacepotential/epicardial potential transformation. In other examples, modeltorso-surface potentials may be simulated based on the analyticrelationship approach to determining the cardiac transmembrane potentialfrom torso-surface potential. Cardiac activation times (parameters inthe analytic relationship) may be computed based on minimizing the leastsquare difference between the projected model torso-surface potentialsand simulated torso-surface potentials.

In some examples, the construction of a torso-surface activation timesisochrone map (1014), wavefront animation (1016), or other graphicalrepresentation of cardiac electrical dyssynchrony, as well as thecalculation of indices of cardiac electrical dyssynchrony (1018), may beperformed for a particular region of the model heart based the computedcardiac activation times in such regions. Graphical representations andindices of cardiac electrical dyssynchrony may be determined for each ofa plurality of regions based on the computed cardiac activation times insuch regions. In some examples, the representations and indices forvarious regions may be presented together or compared.

FIG. 11 is a flow diagram illustrating an example technique formeasuring the cardiac electrical dyssynchrony of a patient viadetermined cardiac activation times. The techniques may comprisedetermining the location of a plurality of electrodes (1100), projectingthe location of the electrodes onto the surface of a model torso (1102),recording the output of the plurality of electrodes (1104), projectingthe output of the plurality of the electrodes on the surface of themodel torso (1106), solving the inverse problem (1108) and determiningthe cardiac activation times for a model heart from the projectedtorso-surface potentials (1110). The cardiac activation times may bedisplayed (1112). One or more indices of electrical dyssynchrony may becalculated (1114). The output, the indices of cardiac electricaldyssynchrony and cardiac activation time maps, may be monitored,allowing a user to diagnose the patient, adjust the position of CRTelectrodes during implantation (1118), or adjust A-V or V-V pacingintervals of the CRT device (1120).

A user may monitor the output of the calculations (1116), e.g., the atleast one indices of cardiac electrical dyssynchrony or the display ofcardiac activation times. Monitoring these values may allow the user todiagnose a condition that might benefit from CRT or to evaluate theeffectiveness of CRT. For example, the at least one index of cardiacelectrical dyssynchrony may indicate the presence of damage toelectrical conductivity of the heart of the patient, for example thepresence of a left or right bundle branch block, that may not beapparent from the examination of a standard 12 lead ECG readout. A largeSDAT indicates that the activation of the ventricles is occurring over alarge time span, indicating that the depolarization of the ventricles isnot occurring simultaneously. A large RAT also indicates a broad rangeof activation times and asynchronous contraction of the ventricles. Ahigh PLAT may indicate that a specific region of the heart, e.g., theposterior regions more associated with the left ventricle, is failing toactivate in concert with the measured QRS complex.

The user may adjust the positioning of CRT electrodes, e.g., electrodes108, 110, and 112 of IMD 100 (FIG. 1) according to the displayed cardiacactivation times or the indices of cardiac electrical dyssynchrony. Forexample, the processing unit, via a display, may implement system thatdisplays shifting colors based on the percentage change of the indicesof cardiac electrical dyssynchrony. As the position of the CRTelectrodes are adjusted (1118), the displayed colors may shift from redto yellow to green based on the percentage improvement of the indices ofcardiac electrical dyssynchrony. This may allow a user to rapidlydetermine if the adjustments of the CRT electrodes are having a positiveeffect on the symptoms of the patient. In another example, the user mayadjust the A-V or V-V pacing intervals of an implanted CRT device (118).The minimum value of the indices of cardiac electrical dyssynchrony mayindicate adequate pacing intervals. Isochrone maps or wave frontpropagation movies may also be used to aid in CRT adjustments or todiagnose conditions that may be responsive to CRT treatment.

As indicated above, to facilitate evaluating the whether a patient is acandidate for CRT based on the monitored output (1116), the one or moreindications of cardiac electrical dyssynchrony, e.g., indices orgraphical indications, may be determined based on torso-surfaceactivation times during both intrinsic conduction of the heart, andduring CRT. Differences between the indications during intrinsicconduction and CRT may indicate that CRT would provide benefit for thepatient, e.g., that the patient is a candidate for CRT. Furthermore,during implantation or a follow-up visit, the one or more indications ofcardiac electrical dyssynchrony may be determined for each of aplurality of lead positions, electrode configurations, or otherparameter values based on torso-surface activation times resulting fromdelivery of CRT at the positions, or with the electrode configurationsor parameter values. In this manner, differences between cardiacelectrical dyssynchrony indications associated with various locations,electrode configurations, or parameter values may be compared todetermine preferred locations, configurations, or values.

Various examples of this disclosure have been described. However, one ofordinary skill in the art will appreciate that various modifications maybe made to the described embodiments without departing from the scope ofthe claims. For example, although SDAT, RAT and PLAT have been discussedas example statistical indices of the dispersion of activation times,other indices or metrics of the dispersion of the timing ofdepolarization may be determined according the techniques of thisdisclosure. As one example, a range of activation times between twospecific regions, e.g., anterior and posterior, may be determined. Asanother example, a range or variability of activation times afterexcluding certain locations or regions may be determined according tothe techniques of this disclosure. The excluded locations or regions maybe those that are believed to be scar tissue, e.g., identified by lowamplitude electrical signals, or locations or regions that are beyondthe extent of the far-field QRS complex. In general, calculation of anindex may include determining any statistical or other value based onthe torso-surface or cardiac activation times, or some subset thereof.These and other examples are within the scope of the following claims.

The invention claimed is:
 1. A method comprising: receiving, with aprocessing unit, a torso-surface potential signal from each electrode ofa plurality of electrodes distributed on a torso of a patient, whereinreceiving the torso-surface potential signal from each electrodecomprises: receiving first torso-surface potential signals sensed duringintrinsic conduction of the heart of the patient; and receiving secondtorso-surface potential signals sensed during cardiac resynchronizationtherapy (CRT) pacing of the heart of the patient; for each electrode ofat least a subset of electrodes of the plurality of electrodes,calculating, with the processing unit, a torso-surface activation timebased on the torso-surface potential signal sensed from the electrode,wherein calculating the torso-surface activation times comprises:calculating first torso-surface activation times based on the firsttorso-surface potential signals; and calculating second torso-surfaceactivation times based on the second torso-surface potential signals,and determining, with the processing unit, an indication of a degree ofelectrical dyssynchrony of a heart of the patient based on thecalculated torso-surface activation times, wherein the indicationcomprises a value that quantifies the degree of electrical dyssynchronyof the heart, and wherein determining the indication of the degree ofelectrical dyssynchrony of the heart of the patient based on thecalculated torso-surface activation times comprises determining a changein electrical dyssynchrony between first torso-surface activation timesand the second torso-surface activation times; and presenting, by theprocessing unit, to a user, the indication of the degree of electricaldyssynchrony via a display, wherein presenting the indication of thedegree of electrical dyssynchrony comprises presenting an indication ofthe change in electrical dyssynchrony.
 2. The method of claim 1, whereindetermining the indication of the degree of electrical dyssynchrony ofthe heart of the patient based on the calculated torso-surfaceactivation times further comprises calculating at least one index ofelectrical dyssynchrony of the heart based on the torso-surfaceactivation times, the indication comprising the index of electricaldyssynchrony, and wherein presenting the indication of the degree ofelectrical dyssynchrony comprises presenting the calculated index to theuser.
 3. The method of claim 2, further comprising: comparing, with theprocessing unit, the first torso-surface activation times duringintrinsic conduction of the heart to the second torso-surface activationtimes during CRT pacing of the heart, wherein calculating the at leastone index of electrical dyssynchrony comprises calculating the at leastone index of electrical dyssynchrony based at least on comparing thefirst torso-surface activation times during intrinsic conduction of theheart to the second torso-surface activation times during CRT pacing ofthe heart.
 4. The method of claim 2, wherein calculating the at leastone index of electrical dyssynchrony comprises calculating a standarddeviation index (SDAT) computed as a standard deviation of thetorso-surface activation times.
 5. The method of claim 2, whereincalculating the at least one index of electrical dyssynchrony comprisescalculating a range of activation times (RAT), wherein calculating theRAT comprises: determining a maximum of the torso-surface activationtimes; determining a minimum of the torso-surface activation times; anddetermining a difference between the maximum of the torso-surfaceactivation times and the minimum of the torso-surface activation times.6. The method of claim 2, wherein calculating the at least one index ofelectrical dyssynchrony comprises calculating a percentage of lateactivation times (PLAT), wherein calculating the PLAT comprises:determining a QRS complex duration; and determining a percentage of thetorso-surface activation times within a region of the torso that arelater than a percentage of the QRS complex duration.
 7. The method ofclaim 2, wherein calculating the at least one index of electricaldyssynchrony comprises: calculating a first index of electricaldyssynchrony for a first region of the torso based on torso-surfaceactivation times from the first region of the torso; and calculating asecond index of electrical dyssynchrony for a second region of the torsobased on torso-surface activation times from the second region of thetorso.
 8. The method of claim 2, wherein calculating the at least oneindex of electrical dyssynchrony comprises: calculating a first set oftwo or more indices of electrical dyssynchrony for a first region of thetorso based on torso-surface activation times from the first region ofthe torso; and calculating a second set of two or more indices ofelectrical dyssynchrony for a second region of the torso based ontorso-surface activation times from the second region of the torso. 9.The method of claim 2, wherein calculating the at least one index ofelectrical dyssynchrony comprises, for each of several regions of thetorso, calculating a set of two or more indices of electricaldyssynchrony for the region of the torso based on torso-surfaceactivation times from region of the torso.
 10. The method of claim 1,wherein presenting the indication of the degree of electricaldyssynchrony of the heart of the patient further comprises: calculatinga torso-surface activation time isochrone map based on the calculatedtorso-surface activation times, wherein the isochrones map depicts aspatial distribution of torso-surface activation times; and presentingthe torso-surface activation time isochrone map via the display.
 11. Themethod of claim 1, wherein presenting the indication of the degree ofelectrical dyssynchrony of the heart of the patient further comprises:calculating a wave front animation based on the calculated torso-surfaceactivation times, wherein the wave front animation depicts a spatialprogression of the activation of the heart; and presenting the wavefront animation via the display.
 12. The method of claim 1, whereinpresenting the indication of the degree of electrical dyssynchrony ofthe heart of the patient comprises displaying one of a plurality ofpredefined colors, each of the colors indicating a respective degree ofthe change of electrical dyssynchrony.
 13. The method of claim 1,wherein presenting the indication of the degree of electricaldyssynchrony of the heart of the patient comprises presenting theindication during an implantation procedure for a cardiacresynchronization therapy (CRT) device.
 14. The method of claim 1,wherein presenting the indication of the degree of electricaldyssynchrony of the heart of the patient comprises presenting theindication during an adjustment procedure for a cardiacresynchronization therapy (CRT) device.
 15. The method of claim 1,wherein presenting the indication of the degree of electricaldyssynchrony of the heart of the patient comprises presenting theindication during a screening procedure to determine if a given patientmight benefit from implantation of a cardiac resynchronization therapy(CRT) device.
 16. The method of claim 1, wherein calculating, for eachelectrode of the at least the subset of electrodes, the torso-surfaceactivation time comprises determining an electrical activation time of aregion of the heart of the patient associated with the electrode basedon the torso-surface potential signal received from the electrode. 17.The method of claim 16, wherein determining the electrical activationtime of the region of the heart of the patient associated with theelectrode based on the torso-surface potential signal comprises solvingan inverse problem of electrocardiography.
 18. A system comprising: aplurality of electrodes distributed on a torso of a patient; and aprocessing unit configured to receive a torso-surface potential signalfrom each electrode of the plurality of electrodes, calculate, for eachelectrode of at least a subset of electrodes of the plurality ofelectrodes, a torso-surface activation time based on the torso-surfacepotential signal sensed from the electrode, and determine an indicationof a degree of electrical dyssynchrony of a heart of the patient basedon the calculated torso-surface activation times, wherein the indicationcomprises a value that quantifies the degree of electrical dyssynchronyof the heart, wherein the torso-surface potential signal comprises firsttorso-surface potential signals sensed during intrinsic conduction ofthe heart of the patient and second torso-surface potential signalssensed during cardiac resynchronization therapy (CRT) pacing of theheart of the patient, wherein the processing unit is configured tocalculate the torso-surface activation times by at least calculatingfirst torso-surface activation times based on the first torso-surfacepotential signals and calculating second torso-surface activation timesbased on the second torso-surface potential signals, and wherein theindication of the degree of dyssynchrony comprises an indication of achange in electrical dyssynchrony between first torso-surface activationtimes and the second torso-surface activation times.
 19. The system ofclaim 18, further comprising a display, wherein the processing unit isfurther configured to: calculate at least one index of electricaldyssynchrony of the heart based on the torso-surface activation times,the indication comprising the index of electrical dyssynchrony; andpresent the calculated index to a user via the display.
 20. The systemof claim 19, wherein the processing unit is further configured to:compare the first torso surface activation times during intrinsicconduction of the heart to the second torso-surface activation timesduring CRT pacing of the heart; and calculate the at least one index ofelectrical dyssynchrony based at least on comparing the first torsosurface activation times during intrinsic conduction of the heart to thesecond torso-surface activation times during CRT pacing of the heart.21. The system of claim 19, wherein the at least one index of electricaldyssynchrony comprises a standard deviation index (SDAT), and whereinthe processing unit is configured to calculate the standard deviationindex (SDAT) by at least determining a standard deviation of thetorso-surface activation times.
 22. The system of claim 19, wherein theat least one index of electrical dyssynchrony comprises a range ofactivation times (RAT), and wherein the processing unit is configured tocalculate the range of activation times (RAT) by at least determining amaximum of the torso-surface activation times, determining a minimum ofthe torso-surface activation times, and determining a difference betweenthe maximum of the torso-surface activation times and the minimum of thetorso-surface activation times.
 23. The system of claim 19, wherein theat least one index of electrical dyssynchrony comprises a percentage oflate activation times (PLAT), and wherein the processing unit isconfigured to calculate the percentage of late activation times (PLAT)by at least determining a QRS complex duration and determining apercentage of subset of the torso-surface activation times within aregion of the torso that are later than a percentage of the QRS complexduration.
 24. The system of claim 19, wherein the processing unit isconfigured to: calculate a first index of electrical dyssynchrony for afirst region of the torso based on torso-surface activation times fromthe first region of the torso; and calculate a second index ofelectrical dyssynchrony for a second region of the torso based ontorso-surface activation times from the second region of the torso. 25.The system of claim 19, wherein the processing unit is configured to:calculate a first set of two or more indices of electrical dyssynchronyfor a first region of the torso based on torso-surface activation timesfrom the first region of the torso; and calculate a second set of two ormore indices of electrical dyssynchrony for a second region of the torsobased on torso-surface activation times from the second region of thetorso.
 26. The system of claim 18, further comprising a display, whereinthe processing unit is configured to: calculate a torso-surfaceactivation time isochrone map based on the calculated torso-surfaceactivation times, wherein the isochrones map depicts a spatialdistribution of torso-surface activation times; and present thetorso-surface activation time isochrone map via the display.
 27. Thesystem of claim 18, further comprising a display, wherein the processingunit is configured to: calculate a wave front animation based on thecalculated torso-surface activation times, wherein the wave frontanimation depicts a spatial progression of the activation of the heart;and present the wave front animation via the display.
 28. The system ofclaim 18, wherein the processing unit is configured to present theindication of the degree of electrical dyssynchrony by at leastdisplaying, via the display, one of a plurality of predefined colors,each of the colors indicating a respective degree of the change ofelectrical dyssynchrony of the heart of the patient.
 29. The system ofclaim 18, wherein the processing unit is configured to calculate, foreach electrode of the at least the subset of electrodes, thetorso-surface activation time by at least determining an electricalactivation time of a region of the heart of the patient associated withthe electrode based on the torso-surface potential signal received fromthe electrode.
 30. The system of claim 18, further comprising a display,wherein the processing unit is configured to present to a user, via thedisplay, the indication of the degree of dyssynchrony of thetorso-surface activation times.
 31. A non-transitory computer-readablestorage medium comprising instructions that, when executed, cause aprocessor to: receive a torso-surface potential signal from eachelectrode of a plurality of electrodes distributed on a torso of apatient by at least: receiving first torso-surface potential signalssensed during intrinsic conduction of the heart of the patient; andreceiving second torso-surface potential signals sensed during cardiacresynchronization therapy (CRT) pacing of the heart of the patient;calculate, for each electrode of at least a subset of electrodes of theplurality of electrodes, a torso-surface activation time based on thetorso-surface potential signal sensed from the electrodes, wherein theinstructions, when executed, cause the processor to calculate thetorso-surface activation time by at least: calculating firsttorso-surface activation times based on the first torso-surfacepotential signals; and calculating second torso-surface activation timesbased on the second torso-surface potential signals; determine anindication of a degree of electrical dyssynchrony of a heart of thepatient based on the calculated torso-surface activation times, whereinthe indication comprises a value that quantifies the degree ofelectrical dyssynchrony of the heart wherein the instructions, whenexecuted, cause the processor to determine the indication of the degreeof electrical dyssynchrony by at least determining a change in inelectrical dyssynchrony between first torso-surface activation times andthe second torso-surface activation times; and present to a user, theindication of the degree of electrical dyssynchrony via a display by atleast presenting an indication of the change in electrical dyssynchrony.32. The non-transitory computer-readable medium of claim 31, wherein theinstructions, when executed, cause the processor to calculate, for eachelectrode of the at least the subset of electrodes, the torso-surfaceactivation time by at least determining an electrical activation time ofa region of the heart of the patient associated with the electrode basedon the torso-surface potential signal received from the electrode.